Amivantamab and lazertinib in patients with EGFR-mutant non–small cell lung (NSCLC) after progression on osimertinib and platinum-based chemotherapy: Updated results from CHRYSALIS-2.

Background: Initial results with the amivantamab (ami) and lazertinib (laz) regimen showed encouraging efficacy in patients (pts) whose disease progressed after standard-of-care osimertinib (osi) and platinum-based chemotherapy (pt-chemo; Shu Ann Oncol 2021; 32:S949-1039; 1193MO). We present updated results of this population (Cohort A) from the CHRYSALIS-2 study (NCT04077463). Methods: Cohort A evaluated ami and laz in pts with EGFR exon 19 deletion or L858R NSCLC whose disease progressed on 1st/2nd-line osi followed by pt-chemo as last line of therapy (target population, n=106) and among a more heavily-pretreated population (n=56) whose disease progressed after osi and pt-chemo ± other therapies without regard to number and sequence of these therapies. Pts received 1050 mg IV ami (1400 mg, ≥80 kg) + 240 mg oral laz. Investigator (INV)- and blinded independent central review (BICR)-assessed response per RECIST v1.1 is reported for efficacy-evaluable pts, defined as pts who initiated study treatment on or before 17 Mar 2021, allowing for ≥6 mo of follow-up for response durability. Results: As of 6 Nov 2021, 162 pts were enrolled in Cohort A (median 62 y, 65% women, 61% Asian, median 3 [range, 2–14] prior lines). Median time between last osi treatment to first dose of ami + laz was 6.3 mo and 2.0 mo for the target and heavily-pretreated populations, respectively. Of 50 efficacy-evaluable pts in the target population, the overall response rate (ORR) by BICR was 36% (95% CI, 23–51), with 1 complete response (CR) and 17 partial responses (PRs), and the clinical benefit rate (CBR) was 58% (95% CI, 43–72); full results for all enrolled pts will be reported at the meeting. Median duration of response (mDOR) was not reached based on BICR. At a median follow-up of 8.3 mo, 7 responders (39%) have achieved a DOR lasting ≥6 mo by BICR. INV-assessed responses were consistent with BICR. Of 56 efficacy-evaluable pts in the heavily-pretreated population (8.7-mo median follow-up), ORR by INV was 29% (95% CI, 17–42), with 1 CR and 15 PRs. CBR was 55% (95% CI, 42–69) and mDOR was 8.6 mo (95% CI, 4.2–NR). BICR results are pending. Preliminary evidence of CNS antitumor activity was reported among 8 pts with baseline brain lesions (7 non-target, 1 target) who had not received radiation within 1 year prior to study enrollment. Most frequent adverse events (AE) were infusion-related reaction (65%), paronychia (49%), rash (41%), and stomatitis (39%). Most common grade ≥3 treatment-related AEs (TRAEs) were infusion-related reactions (7%), acneiform dermatitis (5%), and hypoalbuminemia (4%). TRAEs leading to discontinuation of either or both ami and laz occurred in 12% and 7%, respectively. Conclusions: Among an unselected population that has exhausted SOC osi and pt-chemo, ami and laz demonstrates encouraging antitumor activity with a manageable safety profile. Clinical trial information: NCT04077463